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Crystalline and Amorphous forms of (1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl) octahydrocyclopenta [c]pyrrole-1-carboxylic acid

IP.com Disclosure Number: IPCOM000212330D
Publication Date: 2011-Nov-07
Document File: 5 page(s) / 131K

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The IP.com Prior Art Database

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Crystalline and Amorphous forms of (1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl) octahydrocyclopenta [c]pyrrole-1-carboxylic acid

(1S,3aR,6aS)-2- ((S)-2-((S)-2-cyclohexyl-2- (pyrazine-2-carboxamido) acetamido)-3 ,3-dimethylbutanoyl) octahydrocyclopenta [c]pyrrole-1-carboxylic acid, has the following chemical structure:

It can be used as an intermediate in the preparation of (1S,3aR,6aS)-N-(1(S)-(2-(Cyclopropylamino)oxalyl)butyl)-2-(N-(pyrazin-2-ylcarbonyl)-L-cyclohexylglycyl-3-methyl-L-valyl)perhydrocyclo­penta[c]­pyrrole-1-carboxamide.

Provided are processes for its crystallization.

Form I:

(1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid [10 g] was dissolved in Toluene [50-60 ml] at 55 oC. The obtained clear solution was gradually cooled to 0 oC and maintained at this temperature for 16h. The obtained precipitate was collected by suction filtration, dried in vacuum at 40 oC for 24h to provide the crystallized material in 95% yield which was characterized by XRPD pattern and found to be Form I.

The XRD pattern is presented in the following representative X-ray diffractogram:

CPS

 

 
 

°2theta

 
 

Main XRD peaks are: 7.8, 14.5, 14.8, 15.9, 16.8, 17.5, 18.3, 18.9, 23.4, and 24.4± 0.2 degrees 2-theta. The positions of the peaks were corrected respectively. (No correction was performed on the presented diffractograms in the figure).

From II:  

(1S,3aR,6aS)-2- ((S)-2-((S)-2-cyclohexyl-2- (pyrazine-2- carboxamido) acetamido)-3 ,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid [2 g] was dissolved in EtOAc [20 ml] at 55 oC. The obtained clear solution was gradually cooled to RT followed by addition of Heptane [10 ml]. The resulting mixture was cooled to 0 oC and maintained at this temperature for 16h. The obtained precipitate was collected by suction filtration, dried in vacuum at 40 oC for 24h to provide the crystallized material in 77% yield which was characterized by XRPD pattern and found to be Form II.

The XRD pattern is presented in the following representative X-ray diffractogram:

CPS

 

°2theta

 

Main XRD peaks are: 9.4, 10.1, 11.9, 14.4, 15.9, 17.7, 19.0, 19.9 and 23.5± 0.2 degrees 2-theta. The positions of the peaks were corrected respectively. (No correction was performed on the presented diffractograms in the figure).

Form III:

(1S,3aR,6aS)-2- ((S)-2-((S) -2-cyclohexyl-2- (pyrazine-2-carboxamido) acetamido)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid [4 g] was dissolved in EtOAc [20 ml] at 75 oC. The obtained clear solution was gradually cooled to -10 oC and maintained at this temperature for 16h. The obtained precipitate was collected by suction filtration, dried in vacuum at 40 oC for 24h to provide the crystallized material in 84% yield which was characterized by XRPD pattern and found to be Form III.

The XRD pattern is presented in the following repres...